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Minimal molecule RNA-155 having medical purpose of antiatherosclerotic

An RNA-155, atherosclerosis technology, used in drug combination, drug delivery, pharmaceutical formulation, etc.

Inactive Publication Date: 2011-09-21
ZHEJIANG UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the prevention and treatment of atherosclerosis and coronary heart disease mainly focus on measures such as inhibiting the inflammatory response of atherosclerosis, adjusting blood lipids, inhibiting platelet aggregation, and removing / reducing various risk factors that cause atherosclerosis to progress. According to the inventor's research and search in this field, the current microRNA research on the treatment of atherosclerosis is almost blank

Method used

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  • Minimal molecule RNA-155 having medical purpose of antiatherosclerotic
  • Minimal molecule RNA-155 having medical purpose of antiatherosclerotic
  • Minimal molecule RNA-155 having medical purpose of antiatherosclerotic

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0014] Example 1 Changes in cell biological functions after transfection of miR-155 into THP-1 cells

[0015] The miRNA-155 (SEQ ID NO:2) mimics / inhibitors used in this application for transfection in vitro cell experiments were purchased from ABI Company in the United States, and the agomir-155 (SEQ ID NO:3) used in in vivo animal experiments was purchased In Guangzhou Ruibo Biotechnology Co., Ltd., all are commercial products.

[0016] 1. After miR-155 mimics / inhibitors were transfected, stimulated with oxLDL for 48 hours, Real-time PCR and Northern blot were used to detect the effect of changes in the expression of miR-155 in each group of cells,

[0017] The groups were as follows: blank control group, oxLDL stimulation group alone, negative control group for transfection simulants, negative control group for transfection inhibitors, transfection miR-155 mimic group, transfection miR-155 inhibitor group;

[0018] 2. ELISA detection of changes in inflammatory factors TNF-α...

Embodiment 2

[0022] Example 2 Research on the therapeutic potential of miR-155 at the animal level of atherosclerosis model

[0023] 1. Grouping of experimental animals (male ApoE- / - mice, 12 weeks old) and agomir / antagomir-155 intervention

[0024] 1.1 Screening of cholesterol-modified agomir / antagomir-155 transfection efficiency:

[0025] 1) Identify the transfection efficiency of agomir / antagomir-155 to cells in vitro

[0026] The Cy3-labeled cholesterol-modified and RNA-like reference substance was co-cultured with DC cells, and the concentration gradient was set to 100nmol, 200nmol and 400nmol, and the cell entry efficiency of the cholesterol-modified miRNA negative control without transfection auxiliary reagent was observed by fluorescence microscope ;

[0027] 2) To identify the transfection efficiency of agomir / antagomir to the target tissue in vivo

[0028] The Cy5-labeled cholesterol-modified and RNA-like reference substance was encapsulated with nanoliposomes, and the injecti...

Embodiment 3

[0037] Example 3 Bioinformatics prediction, gene expression profiling Screen miR-155 inflammation-related targets, prove its corresponding mRNA target sequence in cells, and explore its mechanism of action.

[0038] 1. According to the miR-155 target prediction database and its rules, the possible mRNA target sequence of the corresponding miRNA is deduced.

[0039] 2. Use specific miR-155 mimics / inhibitors to act on the cells, and perform gene expression profile chip screening for the altered mRNA:

[0040] Experimental grouping: blank control group, miR-155 mimic treatment group, miR-155 inhibitor treatment group; 24-48 hours after transfection cells, RNA was extracted, and mRNA expression profile chips were used to screen for changes in the mRNA level of cells after miRNA action Variety.

[0041] 3. Combining bioinformatics data, expression profile chip data and the pathological process of AS immune inflammatory response, select the mRNA that is most likely to be the target g...

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Abstract

The invention provides a miRNA-155 used to prepare an antiatherosclerotic medicine. Trough experiments, it is proved in the invention that miRNA-155 has a substantial inhibition effect towards atherosclerotic inflammation no matter on the external cell level or on the internal atherosclerotic module mice level. Because miRNA-155 is a regulation and control molecule in the upstream of genes and simultaneously possesses a plurality of biology functions, so it is very likely that miRNA-155 can become a brand new target point of atherosclerotic treatment. The medicine provided in the invention can effectively prevent nucleic acid from being degraded in organisms, efficiently take an effect on a target organism and can be prepared into compound preparations with other known drugs treating atherosclerotic inflammation such as statins fat-adjusting drug and the like.

Description

technical field [0001] The invention belongs to the field of biotechnology and relates to the application of micromolecule RNA-155 in the preparation of anti-atherosclerosis drugs. Background technique [0002] At present, it is unanimously recognized that atherosclerosis (AS) is a multigene and multifactorial disease, and its pathogenesis is related to inflammation, oxidative stress, apoptosis and hemodynamic changes, and is an extremely complex pathology. process. The instability of AS plaques will lead to serious cardiovascular events, and the immune and inflammatory response plays a key role in the occurrence of AS, especially the stability of plaques. Plaque instability is also affected by many factors. A certain protein or molecular abnormality often cannot reflect the entire pathological process. In the past, traditional methods that only intervene on a certain target gene / protein or a certain transduction pathway have great limitations Therefore, understanding the ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/7105A61K9/08A61K9/10A61K9/14A61K9/20A61P9/10
Inventor 朱建华陈婷严卉杨林郑筱叶
Owner ZHEJIANG UNIV
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